FGF-23 from erythroblasts promotes hematopoietic progenitor mobilization
Abstract
Fibroblast growth factor 23 (FGF-23) hormone is produced by bone-embedded osteocytes and regulates phosphate homeostasis in kidneys. We found that administration of granulocyte colony-stimulating factor (G-CSF) to mice induced a rapid, substantial increase in FGF-23 messenger RNA in bone marrow (BM) cells. This increase originated mainly from CD45−Ter119+CD71+ erythroblasts. FGF-23 protein in BM extracellular fluid was markedly increased during G-CSF–induced hematopoietic progenitor cell (HPC) mobilization, but remained stable in the blood, with no change in the phosphate level. Consistent with the BM hypoxia induced by G-CSF, low oxygen concentration induced FGF-23 release from human erythroblast HUDEP-2 cells in vitro. The efficient mobilization induced by G-CSF decreased drastically in both FGF-23−/− and chimeric mice with FGF-23 deficiency, only in hematopoietic cells, but increased in osteocyte-specific FGF-23−/− mice. This finding suggests that erythroblast-derived, but not bone-derived, FGF-23 is needed to release HPCs from BM into the circulation. Mechanistically, FGF-23 did not influence CXCL-12 binding to CXCR-4 on progenitors but interfered with their transwell migration toward CXCL-12, which was canceled by FGF receptor inhibitors. These results suggest that BM erythroblasts facilitate G-CSF–induced HPC mobilization via FGF-23 production as an intrinsic suppressor of chemoattraction.
Journal
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- Blood
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Blood 137 (11), 1457-1467, 2021-03-18
American Society of Hematology
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Keywords
Details 詳細情報について
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- CRID
- 1050294045368704512
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- NII Article ID
- 120007002610
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- ISSN
- 15280020
- 00064971
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- HANDLE
- 20.500.14094/90008035
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- Text Lang
- en
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- Article Type
- journal article
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- Data Source
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- IRDB
- Crossref
- CiNii Articles
- KAKEN